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Dose painting: Can radiotherapy be improved with image driven dose-responses derived from retrospective radiotherapy data?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.ORCID iD: 0000-0002-4603-6338
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

The main aim of curative radiotherapy for cancer is to prescribe and deliver doses that eradicate the tumor and spare the normal healthy tissues. Radiotherapy is commonly performed by delivering a homogeneous radiation dose to the tumor. However, concern have been raised that functional imaging methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can provide a basis for prescribing heterogeneous doses - higher doses in malignant regions of the tumor and less dose where the tumor is less malignant. This form of radiotherapy is called “dose painting” and has the aim of utilizing the radiant energy as efficiently as possible to increase the tumor control probability (TCP) and to reduce the risk for unwanted side effects of the neighboring normal tissues.

In this project we have studied how dose painting prescriptions could be derived through retrospectively analyzing pre-RT image data and post-RT outcomes for two different patient groups: one diagnosed with head and neck cancer with pre-RT fluorodeoxyglucose (18F-FDG) PET image data; and one patient group diagnosed with prostate cancer with pre-RT Gleason score data that were constructed to be mapped from apparent diffusion coefficient (ADC) data acquired from MRI. The resulting dose painting prescriptions for each of these diagnoses indicated that the TCP could be increased without increasing the average dose to the tumor volumes as compared to homogeneous dose treatments. These TCP increases were more noticeable when the tumors were larger and more heterogeneous than for smaller and more homogeneous tumors.

We have also studied the potential to realize TCP increases with dose painting in comparison to homogeneous dose treatments by optimizing clinically deliverable dose painting plans for both diagnoses, i.e. head and neck cancer and prostate cancer. These plans were optimized with minimax optimization that aimed to maximize a robust TCP increase by considering uncertainties of the patient geometry. These plan optimizations indicated that the TCP compared to homogeneous dose treatments was increasing and robust regarding uncertainties of the patient geometry.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 56
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1603
Keywords [en]
Radiotherapy, functional imaging, dose painting, dose painting by numbers, robust optimization
National Category
Cancer and Oncology
Research subject
Medical Radiophysics
Identifiers
URN: urn:nbn:se:uu:diva-393418ISBN: 978-91-513-0776-3 (print)OAI: oai:DiVA.org:uu-393418DiVA, id: diva2:1360490
Public defence
2019-11-29, Hedstrandsalen, Akademiska Sjukhuset, Ingång 70, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2019-11-08 Created: 2019-10-14 Last updated: 2019-11-08
List of papers
1. Dose painting by numbers based on retrospectively determined recurrence probabilities
Open this publication in new window or tab >>Dose painting by numbers based on retrospectively determined recurrence probabilities
2017 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, p. 236-241Article in journal (Refereed) Published
Abstract [en]

Background and purpose: The aim of this study is to derive "dose painting by numbers" prescriptions from retrospectively observed recurrence volumes in a patient group treated with conventional radiotherapy for head and neck squamous cell carcinoma. Materials and methods: The spatial relation between retrospectively observed recurrence volumes and pre-treatment standardized uptake values (SUV) from fluorodeoxyglucose positron emission tomography (FDG-PET) imaging was determined. Based on this information we derived SUV driven dose-response functions and used these to optimize ideal dose redistributions under the constraint of equal average dose to the tumor volumes as for a conventional treatment. The response functions were also implemented into a treatment planning system for realistic dose optimization. Results: The calculated tumor control probabilities (TCP) increased between 0.1-14.6% by the ideal dose redistributions for all included patients, where patients with larger and more heterogeneous tumors got greater increases than smaller and more homogeneous tumors. Conclusions: Dose painting prescriptions can be derived from retrospectively observed recurrence volumes spatial relation to pre-treatment FDG-PET image data. The ideal dose redistributions could significantly increase the TCP for patients with large tumor volumes and large spread in SUV from FDG-PET. The results yield a basis for prospective studies to determine the clinical value for dose painting of head and neck squamous cell carcinomas.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2017
Keywords
Dose painting, Dose painting by numbers, Dose painting optimization, Head and neck cancer, FDG-PET/CT
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-320782 (URN)10.1016/j.radonc.2016.09.007 (DOI)000395607300011 ()27707505 (PubMedID)
Funder
Swedish Cancer Society, 130632
Note

Correction in: RADIOTHERAPY AND ONCOLOGY, Volume: 131, Pages: 243-243, DOI: 10.1016/j.radonc.2018.11.004

Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2019-10-14Bibliographically approved
2.
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3. Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients
Open this publication in new window or tab >>Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 5, p. 574-581Article in journal (Refereed) Published
Abstract [en]

Background: Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.Methods: The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.Results: The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0-51% for the learning set and by 4-30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.Conclusions: We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Urology and Nephrology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-353194 (URN)10.1080/0284186X.2017.1415457 (DOI)000430114000002 ()29260950 (PubMedID)
Funder
Swedish Cancer Society, 130632
Available from: 2018-06-12 Created: 2018-06-12 Last updated: 2019-10-14Bibliographically approved
4. Robust maximization of tumor control probability for radicality constrained dose painting by numbers of head and neck cancer
Open this publication in new window or tab >>Robust maximization of tumor control probability for radicality constrained dose painting by numbers of head and neck cancer
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(English)In: Article in journal (Refereed) Submitted
Abstract [en]

Background and Purpose The aim of this study was to evaluate the potential and robustness to increase the tumor control probability (TCP) for robustly optimized dose painting plans compared to conventional homogeneous dose plans for head and neck cancers.

Material and Methods We optimized a set of dose painting plans with a robust TCP maximizing objective under different mean dose constraints for the primary clinical target volume (CTVT). These plans were optimized with the robust mini-max algorithm together with dose-responses driven by standardized uptake values (SUV) from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The robustness in TCP was evaluated through sampling treatment scenarios with iso-center displacements. We also analyzed the impact on TCP predictions by considering dose-response uncertainties.

Results The average increase in TCP with dose painting ranged between 3 to 20 percentage points (p.p.) which depended on the allowed integral CTVT dose. The median deviation in TCP increase was below 1p.p. for all sampled treatment scenarios versus the nominal plans. Patients with large tumors and large spread of SUV gained the greatest TCP increases. By considering dose-response uncertainties, a decrease of the TCP for a homogeneous dose yielded an increasing dose painting potential.

Conclusions We have found that it is feasible to optimize FDG-PET driven dose painting plans that robustly increase the TCP compared to homogeneous dose treatments for head and neck cancers. The greatest potential TCP increases were found for patients with larger and more SUV heterogeneous tumors, which may give guidance for patient selection to further test the presented dose painting formalism.

Keywords
Dose painting; Dose painting by numbers; Head and neck cancer; 18F-FDG PET/CT
National Category
Cancer and Oncology
Research subject
Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-394216 (URN)
Funder
Swedish Cancer Society, 130632
Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2019-10-14Bibliographically approved
5. Robust treatment planning of dose painting for prostate cancer based on ADC-to-Gleason score mapping: what is the potential to increase the tumor control probability?
Open this publication in new window or tab >>Robust treatment planning of dose painting for prostate cancer based on ADC-to-Gleason score mapping: what is the potential to increase the tumor control probability?
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background and Purpose

We have in this study evaluated our earlier published dose painting formalism for prostate cancer that is driven by dose-responses of Gleason scores mapped from apparent diffusion coefficient (ADC) image data. The aim of this study is to evaluate the ability to actualize increases of the tumor control probability (TCP) with optimization of “dose painting by numbers” (DPBN) plans in a treatment planning system (TPS) compared to uniform dose treatments for patients with high-risk prostate cancer.

Material and Methods

We have evaluated the potential to actualize TCP increases with realistic DPBN plans as compared to uniform dose treatments for a test set of 17 patients diagnosed with high-risk prostate cancer and pre-RT ADC image data. This potential was evaluated through calculating the DPBN efficiency, defined as the ratio of TCP increases for realistic DPBN plans by TCP increases for ideal DPBN prescriptions. Both the ideal DPBN prescriptions and the realistic DPBN plans were optimized with the objective to maximize the TCP for the target prostate volumes (CTVT) while retaining the same average dose as for conventional uniform dose treatments. For the realistic DPBN plan optimization we tested the impact on the TCP by applying different photon energies, different levels of precision of the mapping of ADC data into Gleason score driven dose-responses, and with respect to different levels of iso-center positioning uncertainties through optimizing with robust minimax optimization.

Results

The median DPBN efficiency for the most conservative planning scenario optimized with 15MV photons, a low precision ADC-to-Gleason mapping, and a robustness distance of 0.6 cm was 10%, meaning that more than half of the patients had a gain in TCP of at least 10% of the TCP for an ideal DPBN prescription. By using 6MV photons, increasing the precision of the ADC-to-Gleason mapping, and decreasing the robustness distance the median of the DPBN efficiency increased by up to 40%.

Conclusions

Optimization of DPBN plans in a TPS can according to our formalism yield TCP increases compared to conventional uniform dose treatments for prostate cancer. These TCP increases are more likely when there is a high precision on the mapping of image data into dose-responses and a high certainty of the tumor position during treatment. These findings motivate further development to ensure accurate and precise mappings of image data into dose-responses and to ensure a high spatial certainty of the tumor position when implementing DPBN in a TPS.

Keywords
Dose painting; Dose painting by numbers; Prostate cancer;
National Category
Cancer and Oncology
Research subject
Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-394217 (URN)
Funder
Swedish Cancer Society, 130632
Available from: 2019-10-05 Created: 2019-10-05 Last updated: 2019-10-14Bibliographically approved

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